METHODS: This is a prospective cohort study done in University Hospital Fertility Clinic for one year duration. A total of 88 euthyroid women who underwent COH as part of planned in-vitro fertilization (IVF) were invited to participate in this study. Serum thyroid function of each women will be monitored before stimulation (T1), day 10-13 of cycle (T2), during oocyte retrieval (T3), one week following embryo transfer (T4), and at four weeks after embryo transfer (T5). Reproductive outcome of IVF will be observed and documented.
RESULTS: Nine women had ongoing singleton pregnancy, seven suffered from miscarriage, while the rest had implantation failure. Serum thyroid-stimulating hormone (TSH) and free thyroxine (fT4) increased throughout stimulation, peaking at 32-36 hours after hCG administration compared to baseline (1.250 vs. 1.740 mIU/L and 13.94 vs. 15.25 pmol/L). It remains elevated until one week following embryo transfer. The increment of serum TSH exceeded the upper limit, acceptable for first trimester (<1.60 mIU/L). However, the evolution of serum TSH and fT4 did not significantly differ with pregnancy outcome.
CONCLUSIONS: In euthyroid women, thyroid function changed significantly during COH, but these changes were not different between the three reproductive outcomes. Thus, we do not suggest continuous thyroid function monitoring during COH.
DESIGN: We measured serum IGF-I and IGFBP-3 levels in a group of Malaysian aborigine children from three jungle settlements; Sinderut and Pos Lanai are known for iodine deficiency and endemic goitre, and Gombak is an iodine replete area with better socioeconomic status.
PATIENTS: A total of 246 children were studied, 188 in the age group 4-10 years and 88 in the age group 11-15 years.
MEASUREMENTS: All children were assessed anthropometrically and height standard deviation score (SDS) were calculated using the CDC Anthropometric Software package. Malnutrition was confirmed clinically and according to the WHO definition of malnutrition. IGF-I and IGFBP-3 were determined by radioimmunoassay, and T4 and TSH by immunoradiometric assay.
RESULTS: Based on the height SDS, Sinderut and Pos Lanai children were significantly more malnourished and stunted than the Gombak children P = 0.0001). T4 levels were significantly lower (P = 0.0001) amongst the 4-10-years old Sinderut (81 +/- 2 nmol/l) than in Pos Lanai (101 +/- 3 nmol/l) or Gombak (123 +/- 3 nmol/l) children. Similar findings were also seen in the older children; mean T4 levels of those from Sinderut and Pos Lanai (83 +/- 3 and 88 +/- 4 nmol/l respectively), were low (P = 0.0001) compared to Gombak (118 +/- 3 nmol/l). Conversely, TSH levels in both age groups of Sinderut children were significantly elevated (P = 0.0001) (3.5 +/- 0.2 and 3.9 +/- 0.3 mU/l respectively) compared to age-matched groups from Pos Lanal (2.1 +/- 0.1 and 2.2 +/- 0.2 mU/l respectively) and Gombak (1.5 +/- 0.1 and 1.5 +/- 0.2 mU/l respectively). IGF-I and IGFBP-3 correlated significantly with the height SDS of the children, In both the 4-10 (r = 0.400, P = 0.0001 and r = 0.365, P = 0.0001 respectively) and 11-15 years age groups (r = 0.324, P = 0.002 and r = 0.533, P = 0.0001 respectively). Correlation between IGFBP-3 and T4 levels was more significant in the younger children (r = 0.412, P = 0.0001). Association between IGF-I and T4 levels was significant only in the 4-10 years age group (r = 0.237, P = 0.001).
CONCLUSIONS: Varying duration and degree of exposure to malnutrition and iodine deficiency resulted in different mean levels of T4, TSH, IGF-I and IGFBP-3 in the three areas. The strong positive associations between IGF-I and IGFBP-3 levels and height SDS suggest that these biochemical measurements are indeed useful indicators of growth and nutritional status in children. The significant correlations between T4 and IGFBP-3 and IGF-1 suggests the importance of thyroid hormones in regulating the synthesis of these growth factors. The age-related increase of these growth factors even amongst malnourished, iodine deficient children implies that age-matched reference ranges are essential for proper evaluation of laboratory results.
METHODS: We studied 50 patients (31 males) with mean age 57 ± 12.2 years who had treatment for NPC between 3 and 21 years (median 8 years) without pre-existing HP disorder from other causes. All patients had a baseline cortisol, fT4, TSH, LH, FSH, oestradiol/testosterone, prolactin and renal function. All patients underwent dynamic testing with insulin tolerance test to assess the somatotroph and corticotroph axes. Baseline blood measurements were used to assess thyrotroph, gonadotroph and lactotroph function.
RESULTS: Hypopituitarism was present in 82% of patients, 30% single axis, 28% two axes, 18% three axes and 6% four axes deficiencies. Somatotroph deficiency was most common (78%) while corticotroph, gonadotroph and thyrotroph deficiencies were noted in 40% (4 complete/16 partial), 22 and 4% of the patients respectively. Hyperprolactinaemia was present in 30% of patients. The development of HP dysfunction was significantly associated with the time elapsed from irradiation, OR 2.5 (1.2, 5.3), p = 0.02, for every 2 years post treatment. The use of concurrent chemo-irradiation (CCRT) compared to those who had radiotherapy alone was also significantly associated with HP dysfunction, OR 14.5 (2.4, 87.7), p < 0.01.
CONCLUSION: Despite low awareness and detection rates, HP dysfunction post-NPC irradiation is common. Use of CCRT may augment time related pituitary damage. As these endocrinopathies result in significant morbidity and mortality we recommend periodic assessment of pituitary function amongst NPC survivors.